Page 244 - Avian Virology: Current Research and Future Trends

Avian Leukosis Virus | 237

generally are considered to have little direct influence on tumour (DCs) during the early stages of differentiation and can trigger
growth. After inoculation of birds with ALV at 4 weeks of age or apoptosis (Liu, D. et al., 2016a). ALV-J inhibits the differentia-
older, transient viraemia was detectable at 1 week and was fol- tion and maturation of DCs and alters cytokine expression that
lowed by antibodies at 3 weeks and later (Maas et al., 1982). In a includes IL-1β, IL-8, and IFN-γ (D. Liu et al., 2016b). Chicken
study of birds naturally infected after hatching, antibodies were macrophages are susceptible to ALV-J, and IL-1β, IL-6, ISG12-1,
first detected at 9 weeks of age, with a marked increase in the and Mx were altered (Lai et al., 2011; Feng et al., 2017).
proportion with antibodies between 14 and 18 weeks, when 80% Congenitally infected chickens do not develop immune
were positive (Rubin et al., 1962). Antibodies against gs-antigen responses to the virus. Instead, they become immunologically
may also occur in ALV-infected birds, but these apparently have no tolerant to the virus and develop a persistent viraemia in the
influence on tumour growth (Roth et al., 1971; Sigel et al., 1971). absence of neutralizing antibodies (Rubin et al., 1962; Meyers,
Knowledge of the occurrence of, and the part played by, cell- 1976). Early infection with ALV-J is particularly likely to induce a
mediated immunity in ALSV infections is still incomplete, but it tolerant infection (Fadly and Smith, 1999; Witter, 2000; Witter et
is likely to be directed against both the virus infection and tumour al., 2000). Birds with a tolerant viraemic infection are more likely
formation. The presence of cytotoxic lymphocytes against viral to develop neoplasms than are immune-infected birds, because of
envelope antigens has been shown in birds immunized with the greater virus load in the viraemic birds.
ALV or RSV (Kurth and Bauer, 1972; Bauer et al., 1976; Bauer Infection by ALV can depress primary and secondary anti-
and Fleischer, 1981), and cell-mediated immunity and the body responses and cell-mediated immunity (Rup et al., 1982)
MHC complex are clearly implicated in the regression of Rous to unrelated antigens, although these effects have been variable
sarcomas (Schat, 1987, 1996). Viral proteins expressed on the in different studies. In congenital infection with the A subgroup
surface of tumour cells appear to be important targets for the cell- RAV-1, B- and T-cell function during the early and late stages of
mediated immunity, and non-virion transformation-specific cell infection were undetectable, although no histological damage to
surface antigens may also be implicated. Thacker and co-workers the bursa, thymus, or spleen was observed (Fadly et al., 1982).
(Thacker et al., 1995) have reported on a new system for study- In contrast, subgroup B ALVs have been reported to induce a
ing MHC-restricted cytotoxic lymphocyte responses to ALV marked suppression of the humoral immune response to several
infection, which should be of value in determining the role of this antigens and decreased responsiveness to several mitogens (Watts
type of cell-mediated immunity in ALV infections. Whether cell- and Smith, 1980). Evidence that subgroup J ALV is immunosup-
mediated immune responses are directed against tumour cells in pressive appears to be equivocal (Stedman et al., 2001, 2000;
lymphoid and other forms of leukosis has yet to be determined. Landman et al., 2002; Zavala et al., 2002). ALV-J infection
Despite major gaps in our understanding of innate immunity induced a strong immune response at 2 weeks of age, but after 4
and adaptive immunity against ALVs for a long time, signifi- weeks of age, the response decreased quickly suggesting that 3–4
cant additional information on the immune responses to ALV weeks post infection is the critical time at which the ALV-J virus
have been gathered from the studies on ALV-J infections. ALV exerts its immunosuppressive effects on the host (Wang, F. et al.,
infection in chickens may be recognized by Toll-like receptor 2011). Nucleotide sequence analysis of consecutive isolates from
7 (TLR-7) and melanoma differentiation-associated gene 5 V+A+ infection profile suggested viral evolution to escape the
(MDA5) (Hang et al., 2014; Li et al., 2015; Feng et al., 2016), host immune response thereby contributing to ALV J persistence
followed by induction of innate immunity including differential (Pandiri et al., 2010). Serum antibodies, which are mainly in the
expression of cytokine and interferon-stimulated genes (ISGs) IgG fraction (Meyers and Dougherty, 1972), are passed on by
(Sabat et al., 2010; Gao et al., 2015; Li et al., 2015; Dai et al., the hen to her progeny via the egg yolk that provides a passive
2016; Feng et al., 2016). It was demonstrated that the increased immunity that lasts 3–4 weeks. Passive antibody delays infection
interleukin-6 (IL-6) is induced by the ALV-J envelope protein by ALV (Witter et al., 1966), reduces the incidence of viraemia
gp85 and capsid protein p27 via PI3K- and NF-κB-mediated sig- and shedding of ALV (Fadly, 1988) and reduces the incidence of
nalling (Gao et al., 2016). The expression of caspase-1 combined tumours (Burmester, 1955). Level and persistence of antibody in
with the inflammasome adaptor NOD-like receptor family, pyrin the chick is related to the titre of antibody in the dam’s serum.
domain-containing 3 (NLRP3), and proinflammatory cytokines
IL-1β and IL-18 increased in ALV-J-infected chick livers (Liu,
+
X.L. et al., 2016). At 3–4 weeks post infection by ALV-J, CD4 Diagnosis
+
T-cell numbers decreased and CD8 T-cell numbers increased
in the infected chicken spleen (F. Wang et al., 2011) indicating Conventional techniques
+
+
that CD4 T-cells may be a primary target for ALV-J with CD8
T-cells playing an important role in host immunity. ALV-A/B/J Virological tests
infection can increase chicken interferon regulatory factors 3 Because different ALV subgroups, including the endogenous
(IRF3) promoter activity in DF-1 cells. DF-1 cells pre-treated retrovirus subgroup E, are widespread among chickens, demon-
with recombinant chicken IFN-α can inhibit the replication of stration of antigen or antibody have limited value in diagnosing
ALV-A/B/J (Dai et al., 2016). It was also found that miR-23b pro- field cases of lymphomas. However, assays for the detection of
motes ALV-J replication by targeting interferon regulatory factor ALV are very useful in identification and classification of new
1 (IRF1) (Li et al., 2015). ALV-J can infect chicken dendritic cells isolates, safety testing of vaccines, and in testing pathogen-free